Inflammation leading to tissue damage is regulated by numerous phlogistic mediators. Since phagocytic leukocytes mast cells contain large numbers and amounts of proteases, they appear to be implicated both in the regulation of inflammation and in the damage incurred during inflammation. Essentially any connective tissue can be degraded by one or more proteases.
Human neutrophils utilize a variety of destructive enzymes during the process of phagocytosis. The major enzymes have been determined to be elastase, cathepsin G, myeloperoxidase and lysozyme.
Rheumatoid arthritis appears to be a disease in which elastase and cathepsin G play a major role in its development. It has now been found that controlling the amount of the destructive enzymes at the site of inflammation can prevent proliferation of the disease and to prevent further associated tissue damage. It has also been found that the administration of alpha 1-antichymotrypsin alone provides a major control of the symptoms of the disease. However, since the cause of disease may be a result of more than one factors, the use of more than one protease inhibitor provides a better chance of success for early remission of the symptoms and for a prophylactic control of the symptoms associated with the disease. Alpha 1-antichymotrypsin when administered with alpha 1-antitrypsin and/or C reactive protein (CRP) provides a reduction in swelling, pain and stiffness.
For chronic cases of rheumatoid arthritis, one form of treatment is that the joint is first flushed with a suitable pharmacological solution such as a saline solution, and then a cocktail of protease inhibitors is administered at the site of inflammation. However, it should be understood that the combination of protease inhibitors can be administered in a single composition or separate individual compositions. The alpha 1-antichymotrypsin being the fastest acting provides the quickest relief of some of the symptoms associated with the disease.
Alpha 1-antichymotrypsin is a naturally occurring protein. As disclosed by Meister P. Nathrath W, "Immunehistochemical Characterization of Histiocytic Tumors" Design Histopathol, 1981; 4:79-87, alpha 1-antichymotrypsin is present within malignant macrophages and has been proposed as a useful immunohistochemical marker for cells of the monocyte/macrophage series.
Chandra et al in their paper entitled, "Sequence Homology Between Human Alpha 1-Antichymotrypsin, Alpha 1-Antitrypsin, and Antithrombin III", Biochemistry, Vol. 22, No. 22, Oct. 25, 1983, p. 5055-5061, which is incorporated herein by reference, discloses one method for the preparation of recombinant of alpha 1-antichymotrypsin for use in the invention.
Alpha 1-antichymotrypsin is a plasma protease inhibitor synthesized in the liver. It is a single glycopeptide chain of approximately 68,000 daltons and belongs to a class of serine protease inhibitors with an apparent affinity toward chymotrypsin-like enzymes. Alpha 1-antichymotrypsin is structurally related to alpha 1-antitrypsin.
Belgian Patent No. 830,629 (1975), which is herewith incorporated by reference, discloses and claims immunologically active compositions characterized by an immunologically effective agent incorporated in a negatively charged liposome. Some of the agents thus encapsulated include virus antigens, bacterial antigens, and the like.
U.S. Pat. No. 4,356,167 to L. A. Kelly, which is incorporated herein by reference, discloses liposome drug delivery systems which may be used in connection with the present invention.
U.S. Pat. No. 4,239,754 to Sache et al, which is incorporated herein by reference, discloses liposome compositions for oral administration.